Progression of cancer is often associated with interactions between cancer cells and the extracellular matrix (ECM). In particular, one major ECM component, hyaluronan (HA), provides a favorable microenvironment for cancer progression. Pancreatic ductal adenocarcinoma (PDAC) is typically characterized by a dense desmoplastic stroma with a large amount of HA, making this molecule as an attractive target for therapy. Several studies have shown efficacy of inhibitors of HA synthesis or signaling for the treatment of PDAC. Recent studies have also demonstrated substantial improvements in the effects of chemotherapy by a targeted depletion of stromal HA in PDAC using an enzymatic agent. Thus, targeting HA has been recognized as a promising therapeutic strategy to treat this highly aggressive neoplasm. In this review article, we summarize our current understanding of the role of HA in the progression of PDAC and discuss possible therapeutic approaches targeting HA.

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We retrospectively analyzed gender differences in clinicopathological features of 20 cases including 4 males with solid pseudopapillary neoplasms (SPN) of the pancreas. Male patients tended to be older than female patients (median age: 39 vs 29 years of age, respectively). While all male patients had no symptoms, half of the female patients had symptoms such as abdominal pain. Thirteen (81%) female patients had a cystic component, and 8 (50%) female patients had calcification. In contrast, only one (25%) male patient each had a cystic component and calcification. Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was 92% (12/13) in female patients and 50% (2/4) in male patients. One male patient was misdiagnosed with a neuroendocrine tumor because the tumor was a clear cell variant of SPN with non-specific immune-positivity for chromogranin A. In one patient of each gender, insufficient specimens were obtained by EUS-FNA. All patients underwent surgical resection. Histologically, one patient of each gender had vascular invasion. None of the patients had lymphadenopathy and distant metastasis. No recurrence has been observed after surgery in all of the patients at present.

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A 24-year-old man was admitted to our hospital because of unconsciousness and very low blood glucose. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a large tumor (11cm) with solid component in the tail of the pancreas. The patient was diagnosed with insulinoma of the pancreatic tail, and laparoscopic distal pancreatectomy was performed. Immunohistochemical examination was positive for insulin and a part was positive for glucagon. The post-operative course was uneventful, and the patient is alive without recurrence at three years and two months.

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A 19-year-old woman, who presented with excessive sweating and hypertension, was diagnosed with multiple pancreatic neuroendocrine tumors (PNET) and adrenal pheochromocytomas. Based on tumors in multiple organs and her family history, we diagnosed von Hippel-Lindau disease. Distal pancreatectomy (body-tail), enucleation of the tumor in the pancreatic head, and adrenalectomy were performed, avoiding total pancreatectomy in terms of preservation of pancreatic function. Histopathological examination revealed multiple PNETs in addition to those recognized before the surgery, but they were thought to be too small to detect. VHL patients often have multiple tumors including PNET synchronously and metachronously, therefore careful consideration of the operative course and follow-up is required.

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